scholarly journals Prediction key genes and the potential molecular mechanism for early recurrent pregnancy loss by Multi-Omics analysis

2020 ◽  
Author(s):  
Le Huang ◽  
Changqiang Wei ◽  
Zhao Zhang ◽  
Jiao Cen ◽  
Zhiwei Zhu ◽  
...  

Abstract Background: The potential mechanism of early recurrent pregnancy loss (ERPL) has not been fully elucidated, a multi-omics analysis can help us find key genes.Results: We download data from Gene Expression Omnibus (GEO), 90 hypermethylation-down regulated genes and 49 hypomethylation-up regulated genes were identified by intersection. Compared with the normal early pregnancy group, the expression of ERCC2 and MLH1 was lower in ERPL group, but the expression of PLEK and FOS was higher, and the expression of MLH1 was statistically significant (p<0.05). Compared with the anembryonic (empty sac) miscarriage group, the expression of MLH1, PLEK, FOS decreased, and that of ERCC2 increased in the embryonic miscarriage group. TF-MDEGs networks predicted SP1, POLR2A, YY1, CREM and CREB1 were involved in methylation regulation of DNA promoter with MDEGs. Among them, YY1, FOXP3 and p53 may be related to the mechanism of MLH1 in ERPL.Conclusions: Our study identified possible aberrant MDEGs, and TF- MDEGs regulatory networks may be related to its mechanism. MLH1 may play an important role in early embryonic development.

2020 ◽  
Author(s):  
Le Huang ◽  
Changqiang Wei ◽  
Zhao Zhang ◽  
Jiao Cen ◽  
Zhiwei Zhu ◽  
...  

Abstract BackgroundThe potential mechanism of early recurrent pregnancy loss (ERPL) has not been fully elucidated, a multi-omics analysis can help us find key genes.ResultsWe download data from Gene Expression Omnibus (GEO), 90 hypermethylation-down regulated genes and 49 hypomethylation-up regulated genes were identified by intersection. Compared with the normal early pregnancy group, the expression of ERCC2 and MLH1 was lower in ERPL group, but the expression of PLEK and FOS was higher, and the expression of MLH1 was statistically significant (p<0.05). Compared with the anembryonic (empty sac) miscarriage group, the expression of MLH1, PLEK, FOS decreased, and that of ERCC2 increased in the embryonic miscarriage group. TF-MDEGs networks predicted SP1, POLR2A, YY1, CREM and CREB1 were involved in methylation regulation of DNA promoter with MDEGs. Among them, YY1, FOXP3 and p53 may be related to the mechanism of MLH1 in ERPL.ConclusionsOur study identified possible aberrant MDEGs, and TF- MDEGs regulatory networks may be related to its mechanism. MLH1 may play an important role in early embryonic development.


2021 ◽  
Vol 104 (1) ◽  
pp. 003685042199727
Author(s):  
Xinyu Wang ◽  
Jiaojiao Yang ◽  
Xueren Gao

Lung adenocarcinoma (LUAD) is the most common histological type of lung cancer, comprising around 40% of all lung cancer. Until now, the pathogenesis of LUAD has not been fully elucidated. In the current study, we comprehensively analyzed the dysregulated genes in lung adenocarcinoma by mining public datasets. Two sets of gene expression datasets were obtained from the Gene Expression Omnibus (GEO) database. The dysregulated genes were identified by using the GEO2R online tool, and analyzed by R packages, Cytoscape software, STRING, and GPEIA online tools. A total of 275 common dysregulated genes were identified in two independent datasets, including 54 common up-regulated and 221 common down-regulated genes in LUAD. Gene Ontology (GO) enrichment analysis showed that these dysregulated genes were significantly enriched in 258 biological processes (BPs), 27 cellular components (CCs), and 21 molecular functions (MFs). Furthermore, protein-protein interaction (PPI) network analysis showed that PECAM1, ENG, KLF4, CDH5, and VWF were key genes. Survival analysis indicated that the low expression of ENG was associated with poor overall survival (OS) of LUAD patients. The low expression of PECAM1 was associated with poor OS and recurrence-free survival of LUAD patients. The cox regression model developed based on age, tumor stage, ENG, PECAM1 could effectively predict 5-year survival of LUAD patients. This study revealed some key genes, BPs, CCs, and MFs involved in LUAD, which would provide new insights into understanding the pathogenesis of LUAD. In addition, ENG and PECAM1 might serve as promising prognostic markers in LUAD.


2020 ◽  
Vol 47 (1) ◽  
pp. 68-76
Author(s):  
Saeideh Hamidian ◽  
Ali Reza Talebi ◽  
Farzaneh Fesahat ◽  
Mohammad Bayat ◽  
Ali Mohammad Mirjalili ◽  
...  

Objective: Since sperm abnormalities are known to be a major reason for recurrent pregnancy loss (RPL), any defects in DNA structure and chromatin condensation can place embryos at risk in the early stage of development and implantation. As antioxidants such as vitamin C may play a protective role against the destruction of protamine genes in sperm chromatin, this study was conducted to evaluate the effects of vitamin C on chromatin and the expression of protamine genes in the male partners of couples with RPL.Methods: Twenty male partners of couples with RPL were selected as the intervention group and received vitamin C supplementation (250 mg daily for 3 months). Healthy fertile men (n=20) were included as controls. Sperm chromatin, DNA integrity, and the expression levels of protamine genes were evaluated before and after treatment.Results: Significant differences were found in sperm morphology, protamine deficiency, and apoptosis between the two groups and before and after vitamin C administration. A significant change was found in mRNA levels of <i>PRM1, PRM2</i>, and the <i>PRM1/PRM2</i> ratio after treatment.Conclusion: Daily oral administration of vitamin C may improve human sperm parameters and DNA integrity by increasing protamine gene expression levels in the male partners of couples with RPL. The beneficial effects of vitamin C supplementation as an antioxidant for the male partners of couples with RPL could lead to improved pregnancy outcomes in these cases.


Andrologia ◽  
2018 ◽  
Vol 51 (1) ◽  
pp. e13171 ◽  
Author(s):  
Vidhu Dhawan ◽  
Manoj Kumar ◽  
Dipika Deka ◽  
Neena Malhotra ◽  
Neeta Singh ◽  
...  

2018 ◽  
Vol 37 (12) ◽  
pp. 982-992 ◽  
Author(s):  
Shuoshan Xie ◽  
Hui Luo ◽  
Huali Zhang ◽  
Honglin Zhu ◽  
Xiaoxia Zuo ◽  
...  

Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 257 ◽  
Author(s):  
Yitong Zhang ◽  
Joseph Ta-Chien Tseng ◽  
I-Chia Lien ◽  
Fenglan Li ◽  
Wei Wu ◽  
...  

Cancer stem cells (CSCs), characterized by self-renewal and unlimited proliferation, lead to therapeutic resistance in lung cancer. In this study, we aimed to investigate the expressions of stem cell-related genes in lung adenocarcinoma (LUAD). The stemness index based on mRNA expression (mRNAsi) was utilized to analyze LUAD cases in the Cancer Genome Atlas (TCGA). First, mRNAsi was analyzed with differential expressions, survival analysis, clinical stages, and gender in LUADs. Then, the weighted gene co-expression network analysis was performed to discover modules of stemness and key genes. The interplay among the key genes was explored at the transcription and protein levels. The enrichment analysis was performed to annotate the function and pathways of the key genes. The expression levels of key genes were validated in a pan-cancer scale. The pathological stage associated gene expression level and survival probability were also validated. The Gene Expression Omnibus (GEO) database was additionally used for validation. The mRNAsi was significantly upregulated in cancer cases. In general, the mRNAsi score increases according to clinical stages and differs in gender significantly. Lower mRNAsi groups had a better overall survival in major LUADs, within five years. The distinguished modules and key genes were selected according to the correlations to the mRNAsi. Thirteen key genes (CCNB1, BUB1, BUB1B, CDC20, PLK1, TTK, CDC45, ESPL1, CCNA2, MCM6, ORC1, MCM2, and CHEK1) were enriched from the cell cycle Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, relating to cell proliferation Gene Ontology (GO) terms, as well. Eight of the thirteen genes have been reported to be associated with the CSC characteristics. However, all of them have been previously ignored in LUADs. Their expression increased according to the pathological stages of LUAD, and these genes were clearly upregulated in pan-cancers. In the GEO database, only the tumor necrosis factor receptor associated factor-interacting protein (TRAIP) from the blue module was matched with the stemness microarray data. These key genes were found to have strong correlations as a whole, and could be used as therapeutic targets in the treatment of LUAD, by inhibiting the stemness features.


2003 ◽  
Vol 17 (4) ◽  
pp. 610-627 ◽  
Author(s):  
Mylene W. M. Yao ◽  
Hyunjung Lim ◽  
Daniel J. Schust ◽  
Sung E. Choe ◽  
Anna Farago ◽  
...  

Abstract Human infertility and recurrent pregnancy loss caused by implantation defects are poorly understood. Hoxa-10-deficient female mice have severe infertility and recurrent pregnancy loss due to defective uterine implantation. Gene expression profiling experiments reveal that Hoxa-10 is an important regulator of two critical events in implantation: stromal cell proliferation and local immunosuppression. At the time of implantation, Hoxa-10 mediates the progesterone-stimulated proliferation of uterine stromal cells. Hoxa-10 mutants express a stromal cell proliferation defect that is accompanied by quantitative or spatial alterations in the expression of two cyclin-dependent kinase inhibitor genes, p57 and p15. Hoxa-10 deficiencyFS also leads to a severe local immunological disturbance, characterized by a polyclonal proliferation of T cells, that occurs in place of the normal progesterone-mediated immunosuppression in the periimplantation uterus.


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